Our research effort involves exploring the cellular mechanisms involved in allograft rejection as well as cellular mechanisms culminating in tolerance induction. Further, we have been particularly interested in cellular immune defects in selected murine immunodeficiency models such as Murine Acquired Immunodeficiency Syndrome (MAIDS), and aging. Our studies encompass a) the role of host type Antigen Presenting Cells (APCs) in allograft rejection: we have shown that host T cells are cross- primed by host APCs that process and present graft alloantigen in association with self-MHC determinants. Cross-priming of host CD4+ T cells (most likely Th cells) is essential for the accelerated rejection seen in engrafted hosts and are currently exploring the role of CD8+ T cells in accelerated rejection responses. Further, we are investigating the use of various drugs to inhibit cross-priming under these conditions, b) the cellular mechanisms by which mice depleted of CD8+ T cells in vivo reject MHC Class I disparate skin grafts: we have demonstrated that rejection is contingent on activation of CD4+ Th cells by additional alloantigens expressed on the graft which in turn activate CD8+ effector cells whose effector function is not blocked by anti-CD8 mAb, c) the mechanism by which primed Th cells mediate accelerated rejection responses, d) the in vivo immunologic deficits in aged mice: we have demonstrated that aged mice have a profound deficit in CD4+ T cell mediated functions but not in CD8+ T cell mediated functions, e) the in vivo immunologic deficits in mice with MAIDS: we have shown that mice infected with a mixture of retroviruses develop deficits in CD4+ T cell mediated functions whereas mice infected with helper-defective retroviruses develop no such immunologic deficits.